Omega-agatoxins: novel calcium channel antagonists of two subtypes from funnel web spider (Agelenopsis aperta) venom.
A new series of polypeptide presynaptic antagonists ("omega-agatoxins") was purified from venom of the funnel web spider Agelenopsis aperta. Physiological data indicate that all of these peptides are antagonists of voltage-sensitive calcium channels. Although all three omega-agatoxins (Aga) described here (omega-Aga-IA, omega-Aga-IB, and omega-Aga-IIA) block insect neuromuscular transmission presynaptically, biochemical data permit their subclassification as Type I and Type II toxins. Type I toxins (omega-Aga-IA and -IB) are 7.5 kDa, have closely related amino acid sequences, and exhibit characteristic tryptophan-like UV absorbance spectra. Complete Edman sequencing of omega-Aga-IA reveals it to be a 66-amino acid polypeptide containing 9 cysteines and 5 tryptophan residues. omega-Aga-IIA, a Type II toxin, is 11 kDa, shows limited amino acid sequence similarity to the Type I toxins, and exhibits mixed tryptophan- and tyrosine-like absorbance. Nanomolar concentrations of omega-Aga-IIA inhibit the specific binding of 125I-labeled omega-conotoxin GVIA to chick synaptosomal membranes while omega-Aga-IA and -IB have no effect under identical conditions. The omega-agatoxins thus are defined as two subtypes of neuronal calcium channel toxins with different structural characteristics and calcium channel binding specificities.
Adams
M E
ME
Department of Entomology, University of California, Riverside 92521.
Bindokas
V P
VP
Hasegawa
L
L
Venema
V J
VJ
D060848:Agatoxins; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001180:Arthropod Venoms / Q000302:isolation & purification* / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000302:isolation & purification* / Q000378:metabolism; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D013056:Spectrophotometry, Ultraviolet; D013111:Spider Venoms / Q000302:isolation & purification* / Q000378:metabolism*
D060848:Agatoxins; D000596:Amino Acids; D001180:Arthropod Venoms; D002121:Calcium Channel Blockers; D013111:Spider Venoms; C060465:omega-agatoxin I